Lithium carbonate is used for the treatment and prophylaxis of affective illnesses. The established practice is to design a treatment regime aimed at achieving a serum lithium concentration (SLC) in the range of 0.6 to 1.0 mmol/liter. For reasons that are yet unknown maintenance of SLC in this range leads to a positive outcome in less than 60 percent of the subjects. It has been suggested that brain lithium concentration (BLC) may be a better prospective indicator of the patient's response to treatment. This hypothesis is supported by the finding that BLC varies considerably in patients with similar SLC. Attempts at measuring BLC non-invasively have relied on the use of magnetic resonance spectroscopy (MRS) to measure the average BLC over large portions of the brain. The use of a large volume of observation in MRS leads to improved signal-to-noise ratio (SNR) but has reduced sensitivity to changes in BLC across the volume of the brain. Observation of these spatial changes in BLC could be of great value for explaining the wide differences in patient responsiveness and for elucidating the mechanisms of action of lithium in the brain. This proposal is aimed at developing a methodology for in vivo three dimensional quantitative lithium imaging using magnetic resonance imaging (MRI). The MRI methodology being proposed compensates for the unfavorable NMR properties of the lithium nucleus and its low concentration in the human brain (0.2-1mM, for patients with SLC in the therapeutic range) through the use of efficient three dimensional data acquisition schemes with short echo times. All the methods are to be developed on a 3.0 Tesla whole body imager using custom-built, high efficiency, dual-tuned (7Li/1H), dual-quadrature birdcage radiofrequency (RF) coils. The quantitative nature of the imaging protocol is to be verified using experimental phantoms of known concentrations and various geometries. After experimental validation, the MRI methodology will be further optimized during imaging trials on a limited number of human subjects from the Western Psychiatric Institute and Clinic of the University of Pittsburgh Medical Center.